Ultrasonic imaging uses an ultrasonic scanner to generate and receive sound waves. A transducer is placed on a body surface overlying the region to be imaged, and ultrasonic energy is directed toward that area. As ultrasonic energy penetrates the body, the velocity of the energy and acoustic properties of the body tissue and organs encountered by the energy determine the degree of absorption, scattering, transmission and reflection of the energy. The characteristics of ultrasonic energy reflected back to the transducer are then transformed into the ultrasonic image.
As ultrasound waves move through one substance to another, there is some degree of reflection at the interfaces. The degree of reflection is related to the acoustic properties of the substances defining the interface. If these properties differ, such as with a liquid-solid or liquid-gas interface, the degree of reflection is enhanced. Body tissues and organs that do not reflect ultrasound energy due to their ability to transmit or absorb the energy appear dark in the image whereas body tissues and organs that reflect the energy appear light in the image. These images may be enhanced by the use of contrast agents.
Imaging of the gastrointestinal tract and surrounding tissues/organs can be difficult due to the presence of acoustically reflective gas bubbles. This problem can be overcome by having the subject ingest a contrast agent which fills the stomach and displaces the gas.
There are two general types of ultrasound contrast agents; positive contrast agents and negative contrast agents. Positive contrast agents reflect the ultrasonic energy and thus they produce a positive (light) image. Correspondingly, negative contrast agents enhance transmissibility or sonolucency and thus produce a negative (dark) image. The sonolucency of an orally administered negative contrast agent contained within the gastrointestinal tract will improve the visualization of the surrounding tissues and organs as well as the tissues defining the gastrointestinal wall.
Several publications disclose orally administered positive contrast agents. A German patent application and article by Helzel (German Pat. Appln. 3246386 A1 and Fortschr. Rontgenstr. (1984) 140:337-340) describe the use of various aqueous emulsions and particulate suspensions as orally administered positive contrast agents. More recently, U.S. Pat. Nos. 5,107,842 and 5,179,995 describe the use of aqueous suspensions, particulate vegetable substances, clays, and hydrocolloids as positive contrast agents. PCT application no. PCT/US91/03850 (Pub. No. WO 91/18612) describes aqueous mixtures of biocompatible polymers, preferably coated with silicon-containing compounds, as orally administered positive contrast agents.
Similarly, there are several prior publications which describe attempts to improve the transmission of ultrasound through the stomach lumen to improve imaging of the stomach wall and upper abdominal organs by filling the stomach with fluids. Stringer et al., J. Ultrasound Med. (1986) 5:183-188 describe ultrasound imaging of children's stomachs into which water with glucose had been introduced. Warren et al., J. Clin. Ultrasound (1978) 6:315-320 report attempts to make the stomach lumen an "ultrasonic window" by filling it with a 1% aqueous mixture of methylcellulose and administering butylscopolamine bromide (Bucospan) i.v. to inhibit peristalsis. The article indicates the methylcellulose forms mucilages in the mixture. While it is reported the mixture "allows good through-transmission of sound", the ultrasound images presented in the article show that the mucilages reflect energy and appear as white granular bodies. Worlicek et al., J. Clin. Ultrasound (1989) 17:5-14 describe ultrasonic imaging of patients who have ingested orange juice and been injected i.v. with butylscopolamine bromide. Miyamoto et al., J. Clin. Ultrasound (1989) 17:309-318 describe ultrasonic imaging of the stomachs of patients who had ingested deaerated water and received a butylscopolamine bromide injection.
These fluids all exhibit rapid gastric emptying thus requiring concomitant injection of an antispasmodic agent to inhibit peristalsis. They also include materials that are echogenic and thus give a positive image (e.g., methylcellulose mucilages, orange juice pulp). In addition they are not chemically defined (orange juice) and thus cannot be expected to provide reproducible enhancement of images.